ECE2014 Poster Presentations Thyroid Cancer (70 abstracts)
The role of the transcription factor: Prospero homeobox 1: in the biology of differentiated thyroid cancer
Magdalena Rudzinska 1 , Damian Gawel 1 , Kamila Karpinska 1 , Miroslaw Kierdrowski 2 , Tomasz Stepien 3 , Magdalena Marchlewska 3 , Hanna Domek 1 & Barbara Czarnocka 1
1Department of Biochemistry and Molecular Biology, Center of Postgraduate Medical Education, Warsaw, Poland; 2Department of Pathology, Institute of Oncology, Maria Sklodowska-Curie Memorial Cancer Center, Warsaw, Poland; 3Department of General and Endocrinological Surgery, Copernicus Memorial Hospital, Lodz, Poland.
One of the pathways of DTC dissemination is the lymphatic system, however the molecular basis of this process is still unknown. One of the key regulators of lymphangiogesis is Prospero homeobox 1 (Prox1) specifically expressed in LEC and in some human cancers. The present study investigates the expression and function Prox1 in biology of differentiated cancer cells.
Studies were performed in a series of thyroid cancer FTC and PTC cell lines. Protein and transcript expression levels and intracellular Prox1 localization were determined using molecular biology methods: Q-RT-PCR, western blot and immunocytochemistry. Overexpression of Prox1 gene was used to determine the role of Prox1 in regulating the hallmarks of malignant cell phenotype (migration, invasion, anchorage independent growth, proliferation and adhesion). We found that Prox1 mRNA and protein were significantly up-regulated in FTC and strongly down-regulated in papillary carcinoma derived cancer cell lines (25-fold). ICC results paralleled Q-RT-PCR and western blot data. Prox1 protein localized in the nucleus or in both cytoplasm and nucleus, depending of cell lines. Prox1 gene overexpression in TPC1 cells negative for Prox1 increased cellular invasion (fourfold), and colony formation in soft agar. The proliferation and adhesion were moderately- or unaffected.
Prox1, a nuclear transcription factor and a ‘master control gene’ of lymphangiogenesis is highly expressed in FTC cell lines whereas in PTC derived cells its level is on the limit of the methods used. Transfection of Prox1 to cells deprived its expression, enhanced malignant cells phenotype by induction of invasiveness and colony formation. This may imply essential role of Prox1 in the regulation of malignant cell phenotype. These findings taken together suggest that Prox1 may be involved in differentiated thyroid cancer progression. Further on-going studies will precisely determine the role of Prox1 lymphangiogenesis factor in DTC biology.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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